Presentation is loading. Please wait.

Presentation is loading. Please wait.

The Defense Medical Research and Development Program Defense Medical Research and Development Program Building the foundation and accelerating the science:

Similar presentations


Presentation on theme: "The Defense Medical Research and Development Program Defense Medical Research and Development Program Building the foundation and accelerating the science:"— Presentation transcript:

1 The Defense Medical Research and Development Program Defense Medical Research and Development Program Building the foundation and accelerating the science: DoD TBI research COL Dallas C. Hack M.D. Brain Health/Fitness Research Program Coordinator US Army Medical Research and Materiel Command June 24, 2014 The views expressed in this presentation are those of the author and do not reflect official policy or position of the Department of the Army, Department of Defense or the U.S. Government. I have no relevant financial relationships to disclose. UNCLASSIFIED

2 COL Dallas C. Hack M.D. UNCLASSIFIED 2 Bottom Line TBI is a continuum of extremely heterogeneic insults to the sub cellular and cellular structure and function of the brain; effects can be life-long Co-morbidities (PTS, Pain, Depression) are more the rule than the exception, complicating study Currently, physical/mental rest and education are the only validated “treatments” and there are no FDA approved therapies Regulatory science is inadequate—a reflection of the state of the science in general. Need for validated “endpoints” for both diagnosis and treatment Because of our limited understanding of the pathobiology, along with a paucity of biomarkers, correlating the human condition with animal models involves a degree of subjective interpretation that is scientifically tenuous and leads to an inability to even compare one model to another The relationships between TBI, neurodegeneration and Chronic Traumatic Encephalopathy are yet to be clearly defined Does recovered mean recovered or does it mean compensated? Because of the inherent complexity of the CNS, we must be prepared for instances where we must dismiss reductionism and use evidence-based “what works” (i.e. some things may simply not be knowable with current technologies) Despite all of the above, we DO find ourselves at a “tipping point” where coordinated foundational efforts will establish the basis for future studies and real, evidence-based progress in the diagnosis and treatment of TBI

3 COL Dallas C. Hack M.D. UNCLASSIFIED 3 TBI Complexity (120,000 foot view) Who is susceptible? What is injured? (Epidemiology/ Pathobiology/ Models) What facilitates recovery? (Epi/Patho/ Models/Metrics) Genetics/ Epi- genetics Co- Morbidities Baseline Function Age & Gender Protective Gear Family History (violence/abuse/ poverty) When was the injury? How was it injured? What are the effects? Resilience Plasticity Policy Therapies Biomarkers/ Metrics General Health/ Education Early Identification & Treatment Clinical Practice Guidelines

4 COL Dallas C. Hack M.D. UNCLASSIFIED 4 Lessons Forgotten and Re-Learned

5 COL Dallas C. Hack M.D. UNCLASSIFIED 5 Lessons Learned & Re-learned

6 COL Dallas C. Hack M.D. UNCLASSIFIED 6 Co-Morbidities Associated with mTBI and PTSD PTSD N= % 2.9% 16.5% 42.1% 6.8% 5.3% 10.3% 12.6% TBI N= % Chronic Pain N= % Lew, et al: “Prevalence of Chronic Pain, Posttraumatic Stress Disorder, and Persistent Postconcussive Symptoms in OIF/OEF Veterans: Polytrauma Clinical Triad”, Dept. of Veterans Affairs, Journal of Rehabilitative Research and Development, Vol. 46, No. 6, 2009, pp , Fig. 1 Traumatic Brain Injury: Comorbidities Accessed 17 Oct 2012 *http://dx.doi.org/ /j.jsr Accessed 13 Mar million * Comorbidity Examples Sleep disordersVestibular disorders Substance abuseVisual disorders Psychiatric illnessCognitive disorders Total: >3.6 million *

7 COL Dallas C. Hack M.D. UNCLASSIFIED 7 Garrison Associated Deployment Associated DoD: Garrison vs. Deployed TBI 83% of all DoD TBIs from occurred away from combat Bottom Line: TBI will remain an military concern long after withdrawal from Afghanistan Number of TBI Cases Worldwide Source: Armed Forces Health Surveillance Center DoD TBI Cases Worldwide

8 COL Dallas C. Hack M.D. UNCLASSIFIED 8 Timeline: Key TBI Policies 2006/ October ASD(HA) released a memorandum providing a standard TBI, severity of brain injury stratification, and a uniform reporting process April Army and USMC revise Purple Heart criteria April Version 3 of MACE released June Army publishes DA EXORD mandating TBI training May DoD requires mandatory cognitive baselines on SMs (NCAT/ANAM) June DTM signed September DoDI published June DoD releases 2012 MACE and Concussion Management Algorithms August MACE implemented May Mandatory TBI screening at LRMC for all MEDEVACs Summer MAJ Bell pilots Concussion Care Center at FOB Shank May USFOR-A Policy Letter #40, Afghanistan Theater Concussive Care April VA-DoD CPGs May NCAT Clinical Recommendation (CR) April-July Driving and Cognitive Rehab CRs August & September Dizziness and neuroendocrine CRs

9 COL Dallas C. Hack M.D. UNCLASSIFIED 9 TBI Theater Policy: Potentially Concussive Events Involvement in a vehicle blast event, collision, or rollover A direct blow to the head or witnessed loss of consciousness Presence within 50 meters of a blast (inside or outside) Exposure to more than one blast event (the Service member’s commander shall direct a medical evaluation) Mandatory 24-hrs downtime, medical eval, and reporting

10 COL Dallas C. Hack M.D. UNCLASSIFIED 10 Theater TBI Medical Guidance 2012 Concussion Management Algorithms (CMAs) 2012 Military Acute Concussion Evaluation (MACE)

11 COL Dallas C. Hack M.D. UNCLASSIFIED 11 Traumatic Brain Injury: 2014 Classification GCS (Glasgow Coma Scale) Outcome GOS (Glasgow Outcome Scale) Mild Severe Concussion Death Vegetative Good Recovery A Complex and Heterogeneous Disease

12 COL Dallas C. Hack M.D. UNCLASSIFIED 12 Disease Classification: Cancer bioinformatic analyses AML ALL Modern disease classification is a mixture of anatomic, cellular, physiologic, metabolic, immunologic, and genetically defined diseases

13 COL Dallas C. Hack M.D. UNCLASSIFIED 13 INJURY OUTCOME A Fragmented Approach to TBI Research Genomics MRI CT PTSD Rehab PET Proteomic Biomarkers EEG

14 COL Dallas C. Hack M.D. UNCLASSIFIED 14 Solution: Integration Across Disciplines and Research Studies Injury Characteristics Time Patient Characteristics

15 COL Dallas C. Hack M.D. UNCLASSIFIED 15 Big Picture Solutions: Collaborative, Integrated, Multidimensional Research Networks NCAA - DOD CENTER- TBI TRACK -TBI C- LEARN NCAA- 15 yr CRC GE- NFL TED CENC Time Patient Characteristics Injury Characteristics

16 COL Dallas C. Hack M.D. UNCLASSIFIED 16 Study Landscape 12 6 MONTHS YEARS TBI TRACK-TBI CENTER-TBI Mission Connect ADNI-DOD NCAA Long term Follow-up (15 yr) INTRuST CENC Canadian Pediatric Mild TBI Study Project Head to Head Army STARRS NCAA-DoD Grand Challenge TED (Endpoints) BTEC Dynamic Model

17 COL Dallas C. Hack M.D. UNCLASSIFIED Brain Trauma Evidence-Based Consortium Current Status of B-TEC Efforts 1. Concussion Guidelines Part 1. Systematic Review of Prevalent Indicators Publication in submission 2. Raw Data Review [RaDaR] First re-analysis of concussed sample [N = 650] complete. Data mining project scheduled for late winter. Draft diagnostic criteria by June. 3. Dynamic Model Initiative First meeting held September Second meeting to be held January 16-17, 2014 [Boston]. 4. Collaborations CENC, NCAA, ACR [Epic], TBI-Trac©, Track-TBI, ADAPT, Latin America. 5. Living Guidelines Completed transition of Pediatric Guidelines to new model. Adult guidelines 4 th edition in process, to be complete by Spring 2014

18 COL Dallas C. Hack M.D. UNCLASSIFIED 18 TBI Endpoints Development A Phased approach involving key research milestones Purpose: to identify endpoints that would be acceptable to the FDA in their regulatory review of drugs and devices that are being developed for use in the clinical setting to diagnose or treat mild TBI to moderate TBI Two Stages: –Stage I (Years 1-2) will enable the team to lay the groundwork for the research and conduct studies required to advance the most promising endpoints –Stage II (Years 3-5) will allow the expansion of the project to proceed to larger-scale validation studies

19 COL Dallas C. Hack M.D. UNCLASSIFIED Database with multiple contributors and multiple accessors A collaboration between NIH and DoD to develop a biomedical informatics system to accelerate scientific discovery and treatment in Traumatic Brain Injury FITBIR Data Repository: Federal Interagency TBI Research

20 COL Dallas C. Hack M.D. UNCLASSIFIED 20 Presidential Executive Order 31 Aug 2012: Improving Health Care for Veterans, Service Members, and Military Families Affected by TBI Sec. 5. Improved Research and Development –DoD, VA, HHS, and Dept of Ed in coordination with the Office of Science and Technology Policy shall establish a National Research Action Plan within 8 months of the date of this order to improve the coordination of agency research of TBI, PTSD, and other mental health conditions to reduce the number of affected men and women through better prevention, diagnosis, and treatment. –National Research Action Plan shall: >Establish strategies to establish surrogate and clinically actionable biomarkers for early diagnosis and treatment effectiveness >Develop improved diagnostic criteria for TBI >Enhance understanding of mechanisms responsible for PTSD, related injuries, and neurological disorders following TBI >Foster development of new treatments for these conditions based on better understanding of underlying mechanisms >Improve data sharing between agencies and academic and industry researchers to accelerate progress and reduce redundant efforts without compromising privacy >Make better use of electronic health records to gain insight into the risk and mitigation of PTSD, TBI, and related injuries >Include strategies to support collaborative research to address suicide prevention

21 COL Dallas C. Hack M.D. UNCLASSIFIED 21 National Research Action Plan Response to President Obama’s 2012 Executive Order Interagency Collaboration: –DoD, VA, HHS, NIDRR (Dept of Education) Key Themes Specific to TBI Research: –Biomarkers: (Imaging, proteomic, neurophysiologic, etc.) to diagnose and monitor recovery –Diagnosis: more precise classification system, personalized/targeted diagnosis –Mechanisms: increase understanding of neuropathology –Treatment: identify and validate pharmacologic and rehabilitation treatment options

22 COL Dallas C. Hack M.D. UNCLASSIFIED 22 Return to Duty/Disability/Reclassification Assessment Continuing Education and Reinforcement for Servicemembers, Leaders and Service Providers Continuum of TBI Care Determines Research Approach RESEARCH NEEDS SOLUTIONS RDT&E: Injury Prevention Combat Casualty Care Psych Health and Related Symptoms 19 studies (8*) $21,235K 51 studies (24*) $97,851K 90 studies (39*) $96,612K 148 studies (64*) $253,492K 6 studies (4*) $4,764K 59 studies (32*) $72,548K 531 studies, active Total investment $720,786K Head Impact/ Blast Injury Sensors and Dosimeters Improved, objective (and standardized) RTD assessments and guidelines Drugs, nutraceuticals, nutrition. neuromodulation : (Cranial Nerve Stimulation) Cognitive, Behavioral, Neurological and Diffusion Tensor Imaging (DTI), Magnetic Resonance Spectroscopy Rehabilitation: Measures/ markers for rehabilitation assessment and development of useful rehab approaches Nutraceuticals, Standards for Helmets, Education/ CPG’s for Servicemembers, Leaders & Service Providers Objective Assessments: Quantitative EEG (qEEG) and smooth pursuit eye tracking. BANDITS= biomarker assessment for neurotrauma diagnosis & improved triage system. Neuropat hology studies of military TBI Cognitive, Behavioral, Motor, Sensory, Endocrine effects; Chronic Traumatic Encephalopathy (CTE) and other neuro- degenerative diseases 13 studies (4*) $45,892K 9. Identify, Monitor for and Treat Late and Chronic Effects 8. Return to Duty 7. TBI/ Concussion Recovery 6. TBI/ Concussion Treatment 5. TBI/ Concussion Assessment 4. TBI/ Concussion Screening (DoD Guidelines 3. Possible Concussive Event (PCE) via Impact or Blast 2. TBI/ Concussion Prevention/ Education & Training Medical Standards for Protective Equipment Objective Measure of Head Impact/Blast Exposure Valid Criteria & Objective Servicemembers/ Concussion Screening Tool Portable Fieldable Diagnostic Device (In Theatre & Garrison) Pharmaceutics & Surgical Technology Recovery Timecourse & Rehabilitation Valid RTD Standards & Measures of Rehabilitation Define and treat co-morbidities and chronic effects 23 October 2013 *Closed Studies as of 1 September studies (8*) $9,193K 1. Basic Science & Epidemiology: 134 studies (77*), $119,199K

23 COL Dallas C. Hack M.D. UNCLASSIFIED 23 DoD Joint Program Committee Strategic Research Planning Process User Needs and State of Practice Analysis Requirement- based Capability Gap Prioritization Research Prioritization Factors (Portfolio Balance, Political, Intramural Lab Capabilities, etc.) Research Prioritization Factors (Portfolio Balance, Political, Intramural Lab Capabilities, etc.) Research Prioritization Strategic Planning Portfolio Analysis Create database Analyze Intramural and Extramural Investments Identify Areas for Resolution Identify Findings for Transition Portfolio Analysis Create database Analyze Intramural and Extramural Investments Identify Areas for Resolution Identify Findings for Transition Implementation Plan Implementation Barriers Analysis (Manpower, Federal Acquisitions Regulation, Budget Related, Size of Portfolio) Implementation Barriers Analysis (Manpower, Federal Acquisitions Regulation, Budget Related, Size of Portfolio) Resource Allocation (DHP, Army, SBIR) Resource Allocation (DHP, Army, SBIR) State of Science/Research Research Gaps Identification Review and Analysis (Army, Navy, Air Force, Marines, VA, ASD/HA, NIH, NIMH, Academic Subject Matter Experts) Review and Analysis (Army, Navy, Air Force, Marines, VA, ASD/HA, NIH, NIMH, Academic Subject Matter Experts) Program Announcements/ Requests for Proposals/Broad Agency Announcement Program Announcements/ Requests for Proposals/Broad Agency Announcement Transition of select Materiel Solutions to Advanced Development Dissemination of knowledge/ Clinical Practice Guidelines

24 COL Dallas C. Hack M.D. UNCLASSIFIED 24 Summary DoD uses a “continuum of care” model to achieve a comprehensive approach Objective diagnostics and pharmaceutical treatment represent the largest areas of research investment Several capabilities have been identified as showing promise for use in the clinic Imaging, neuroplasticity, and rehabilitation represent the nearest promising research investments Objective measures of response to treatment remain a focus for accelerating recovery Partnerships with the VA, NIH, academia, and industry remain vital to success

25 COL Dallas C. Hack M.D. UNCLASSIFIED 25 Questions?


Download ppt "The Defense Medical Research and Development Program Defense Medical Research and Development Program Building the foundation and accelerating the science:"

Similar presentations


Ads by Google